title: In vivo neuroprotective effect of L-carnitine against oxidative stress in maple syrup urine disease.
abstract: Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of metabolism caused by deficiency of the activity of the mitochondrial enzyme complex branched-chain α-keto acid dehydrogenase (BCKAD) leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine and their corresponding branched-chain α-keto acids. Affected patients present severe brain dysfunction manifested such as ataxia, seizures, coma, psychomotor delay and mental retardation. The mechanisms of brain damage in this disease remain poorly understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. L-Carnitine (L-Car) is considered a potential antioxidant through its action against peroxidation as a scavenger of reactive oxygen species and by its stabilizing effect of damage to cell membranes. In this study we evaluate the possible neuroprotective in vivo effects of L-Car against pro-oxidative effects of BCAA in cerebral cortex of rats. L-Car prevented lipoperoxidation, measured by thiobarbituric acid-reactive substances, protein damage, measured by sulfhydryl and protein carbonyl content and alteration on catalase and glutathione peroxidase activity in rat cortex from a chemically-induced model of MSUD. Our data clearly show that L-Car may be an efficient antioxidant, protecting against the oxidative stress promoted by BCAA. If the present results are confirmed in MSUD patients, this could represent an additional therapeutic approach to the patients affected by this disease.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Mescka
authors.forename: Tarsila
authors.initials: T
authors.lastname: Moraes
authors.forename: Andrea
authors.initials: A
authors.lastname: Rosa
authors.forename: Priscila
authors.initials: P
authors.lastname: Mazzola
authors.forename: Bruna
authors.initials: B
authors.lastname: Piccoli
authors.forename: Carlos
authors.initials: C
authors.lastname: Jacques
authors.forename: Giovana
authors.initials: G
authors.lastname: Dalazen
authors.forename: Juliana
authors.initials: J
authors.lastname: Coelho
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cortes
authors.forename: Melaine
authors.initials: M
authors.lastname: Terra
authors.forename: Carmen
authors.initials: C
authors.lastname: Regla Vargas
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Dutra-Filho
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000172:deficiency; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002331:Carnitine / Q000378:metabolism / Q000494:pharmacology; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry* / Q000201:enzymology; D004195:Disease Models, Animal; D005260:Female; D005979:Glutathione Peroxidase / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007651:Keto Acids / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008375:Maple Syrup Urine Disease / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D000975:Antioxidants; D007651:Keto Acids; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D005979:Glutathione Peroxidase; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); D002331:Carnitine